Tert-Butylamine → N-tert-butyl-2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246775Notes

Reaction equation

HRID 246775 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:14])[N:9]=[C:8]2[C:15]1[N:16]=[C:17]2[C:23]([C:24]([OH:26])=O)=[CH:22][NH:21][C:18]2=[N:19][CH:20]=1)(=[O:4])=[O:3].[CH3:27][C:28]([NH2:31])([CH3:30])[CH3:29].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:28]([NH:31][C:24]([C:23]1[C:17]2=[N:16][C:15]([C:8]3[C:7]4[C:11](=[CH:12][CH:13]=[C:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH:6]=4)[N:10]([CH3:14])[N:9]=3)=[CH:20][N:19]=[C:18]2[NH:21][CH:22]=1)=[O:26])([CH3:30])([CH3:29])[CH3:27]

Participants

8

Reactant 5

HCID 6385Tert-ButylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 712795392-(5-methanesulfonyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71280042N-tert-butyl-2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideYield 8.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(5-methanesulfonyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (75 mg, 0.20 mmol), 2-methylpropan-2-amine (15 mg, 0.20 mmol), HOBt (108 mg, 0.80 mmol), EDCI (153 mg, 0.80 mmol) and DIPEA (103 mg, 0.80 mmol) in DMF (6 mL) was stirred at room temperature for 15 hours, then water (30 mL) was added, product extracted with EtOAc (3×30 mL), organics combined dried with sodium sulfate, filtered and concentrated under reduced pressure and residue purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 30% methanol/70% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 50% methanol/50% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.) to give N-tert-butyl-2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (7 mg, 8.1%) as a white solid. LCMS: (M+H)+=427; 1H NMR (300 MHz, CD3OD): δ 9.08 (s, 1H), 8.99 (s, 1H), 8.33 (s, 1H), 8.01 (d, 1H, J=8.7 Hz), 7.90 (d, 1H, J=8.7 Hz), 4.28 (s, 3H), 3.17 (s, 3H), 1.57 (s, 9H).

Workup

  1. extractionproduct extracted with EtOAc (3×30 mL)
  2. dry with materialorganics combined dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure and residue
  5. custompurified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  6. wait30% methanol/70% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 50% methanol/50% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-43cdca4a3cfb446488c61363eaa850d2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…